What is the management of hairy cell leukemia?

Management of Hairy Cell Leukemia

Purine nucleoside analogs (cladribine or pentostatin) are the first-line treatment for symptomatic hairy cell leukemia, achieving complete response rates of 85-91% with a single course of therapy. 1, 2

Initial Treatment Decision

When to Treat

• Treatment is indicated for patients with:
  • Symptomatic disease (fatigue, weight loss)
  • Cytopenias (hemoglobin <11 g/dL, platelets <100 × 10⁹/L, neutrophils <1 × 10⁹/L)
  • Symptomatic splenomegaly or hepatomegaly
  • Recurrent infections
  • Progressive lymphocytosis or lymphadenopathy 2

When to Observe

• Asymptomatic patients without cytopenias should be monitored with regular follow-up every 3-6 months 1, 2

First-Line Treatment Options

Cladribine (2-CdA)

• Preferred agent due to convenience of administration
• Dosing options:
  • Continuous IV infusion: 0.09-0.1 mg/kg/day for 7 days
  • 2-hour IV infusion: 0.12-0.14 mg/kg/day for 5-7 days
  • Subcutaneous injection: 0.1 mg/kg/day for 5-7 days or 0.14 mg/kg/day for 5 days
  • Weekly schedule: 0.12-0.15 mg/kg in 2-hour infusion once weekly for 6 weeks 1
• Efficacy: 87-100% overall response rate with 85-91% complete remission rate 1, 3

Pentostatin (DCF)

• Dosing: 4 mg/m² IV every 2 weeks until complete response, plus 1-2 consolidating injections
• Typically requires 8-9 courses before normalization of blood counts 1
• Similar efficacy to cladribine but less convenient administration 1

Special Considerations

Active Infection

• If active infection is present:
  • Attempt to control infection before administering purine analogs
  • Consider alternative initial therapy with interferon-α, low-dose pentostatin, or vemurafenib to improve neutrophil count before standard purine analog therapy 1, 2

Severe Neutropenia

• For patients with severe neutropenia (neutrophil count <0.2 × 10⁹/L):
  • Consider interferon-α to increase neutrophil count before purine analog therapy 1, 2

Pregnancy

• Interferon-α is preferred over purine analogs during pregnancy 1, 2

Response Evaluation

• Formal assessment should be performed 4-6 months after completion of primary therapy 1, 2
• Complete response (CR) requires:
  • Absence of hairy cells in peripheral blood and bone marrow
  • Normalization of blood counts (hemoglobin >12 g/dL, platelets >100 × 10⁹/L, neutrophils >1.5 × 10⁹/L)
  • Resolution of organomegaly 1
• Partial response (PR) requires:
  • ≥50% reduction in bone marrow hairy cells
  • <5% circulating hairy cells
  • Normalization of peripheral blood counts 1

Management of Partial Response

• If only partial response is achieved after first course of cladribine:
  • Administer a second course at least 6 months after the end of the first course
  • Consider adding rituximab to the second course 1

Management of Relapsed Disease

Second-Line Treatment

• Retreatment with purine analogs is effective at relapse:
  • Overall response rate of 83% in second-line treatment 4
  • Consider combination of purine analog with rituximab for improved outcomes 5, 6
  • Combination therapy achieves 89% complete response rate and significantly lower recurrence rates compared to purine analog monotherapy 6

Refractory/Multiple Relapsed Disease

• Options include:
  • Purine analog + rituximab combination 5, 6
  • Anti-CD22 immunotoxin moxetumomab pasudotox
  • BRAF inhibitors (vemurafenib, dabrafenib) for patients with BRAF-V600E mutation, especially those with or at risk of severe infections 7

Long-Term Outcomes and Follow-Up

• Median progression-free survival after purine analog therapy can extend up to 15 years 5
• Complete responders have significantly better progression-free survival than partial responders (5-year PFS 71% vs. 39%) 4
• Overall survival for treated patients is excellent, with 96% survival at 48 months 8
• Regular follow-up is essential, as approximately half of patients may experience one or more relapses over time 7

Common Pitfalls and Caveats

1. Delaying treatment in symptomatic patients: Initiate treatment promptly in patients with cytopenias or symptoms
2. Administering standard-dose purine analogs during active infections: Control infections first or use alternative agents
3. Inadequate response assessment: Always perform bone marrow biopsy to confirm complete response
4. Overlooking minimal residual disease: Consider eradication of minimal residual disease in select cases, though not routinely recommended
5. Failing to monitor for second malignancies: Long-term follow-up is important as there may be an increased risk of second neoplasms 8